Journal of Anesthesia

, Volume 29, Issue 6, pp 821–830 | Cite as

Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α

  • Hua Liang
  • Cheng Xiang Yang
  • Bin Zhang
  • Han Bing Wang
  • Hong Zhen Liu
  • Xiao Hong Lai
  • Mei Juan Liao
  • Tao Zhang
Original Article
First Online:
Received:
Accepted:

Abstract

Purpose

Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated.

Methods

A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting.

Results

Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia.

Conclusions

Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.

Keywords

Lung cancer cells Hypoxia-inducible factor-1α Sevoflurane 
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Notes

Acknowledgments

This study was supported by Guangdong Province Medicine Scientific Research Fund, Guangdong province, China (B2013372).

Conflict of interest

The authors declare that they have no conflicts of interest concerning this article.

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Copyright information

© Japanese Society of Anesthesiologists 2015

Authors and Affiliations

  • Hua Liang
    • 1
  • Cheng Xiang Yang
    • 1
  • Bin Zhang
    • 1
  • Han Bing Wang
    • 1
  • Hong Zhen Liu
    • 1
  • Xiao Hong Lai
    • 1
  • Mei Juan Liao
    • 1
  • Tao Zhang
    • 1
  1. 1.Department of AnesthesiologyAffiliated FoShan Hospital of SUN YAT-SEN UniversityFoshanChina

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